Ch. 5. Respiratory Physiology.

Question 1

Conducting zone (or conducting airways)

Answer 1

Includes the nose, nasopharynx, larynx, trachea, bronchi, bronchioles, and terminal bronchioles. These structures function to bring air into and out of the respiratory zone for gas exchange and to warm, humidify, and filter the air before it reaches the critical gas exchange region.

The conducting airways are lined with mucus-secreting and ciliated cells that function to remove inhaled particles. Although large particles usually are filtered out in the nose, small particles may enter the airways, where they are captured by mucus, which is then swept upward by the rhythmic beating of the cilia.

Question 2

Respiratory zone

Answer 2

Includes the structures that are lined with alveoli and therefore participate in gas exchange: the respiratory bronchioles, alveolar ducts, and alveolar sacs.

Question 3

Smooth muscle

Answer 3

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Question 4

Dilation

Answer 4

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Question 5

Constriction

Answer 5

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Question 6

Asthma

Answer 6

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Question 7

Gas exhange

Answer 7

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Question 8

Respiratory bronchioles

Answer 8

Transitional structures. Like the conducting airways, they have cilia and smooth muscle, but they also are considered part of the gas exchange region because alveoli occasionally bud off their walls.

Question 9

Alveolar ducts

Answer 9

Completely lined with alveoli, but they contain no cilia and little smooth muscle.

Question 10

Alveolar sacs

Answer 10

The alveolar ducts terminate in alveolar sacs, which are also lined with alveoli.

Question 11

Alveoli

Answer 11

Pouch-like evaginations of the walls of the respiratory bronchioles, the alveolar ducts, and the alveolar sacs.

Each lung has a total of approximately 300 million alveoli, and the diameter of each alveolus is approximately 200 micrometers.

Exchange of oxygen (O2) and carbon dioxide (CO2) between alveolar gas and pulmonary capillary blood can occur rapidly and efficiently across the alveoli because alveolar walls are thin and have a large surface area for diffusion.

The alveolar walls are rimmed with elastic fibers and line with epithelial cells, called type I and type II pneumocytes (or alveolar cells).

Question 12

Type II pneumocytes

Answer 12

Synthesize pulmonary surfactant (necessary for reduction of surface tension of alveoli) and have regenerative capacity for the type I and type II pneumocytes.

Question 13

Pulmonary surfactant

Answer 13

Necessary for reduction of surface tension of alveoli.

Question 14

Alveolar macrophages

Answer 14

Phagocytic cells in the alveoli that keep them free of dust and debris because the alveoli have no cilia to perform this function.

Macrophages fill with debris and migrate to the bronchioles, where the beating cilia carry debris to the upper airways and the pharynx, where it can swallowed or expectorated.

Question 15

Gravitational effects

Answer 15

Because of gravitational effects, pulmonary blood is not distributed evenly in the lungs.

When a person is standing, blood flow is lowest at the apex (top) of the lungs and highest at the base (bottom) of the lungs.

When a person a supine (lying down), these gravitational effects disappear.

Question 16

Regulation of pulmonary blood flow

Answer 16

Accomplished by altering the resistance of the pulmonary arterioles. Changes in pulmonary arteriolar resistance are controlled by local factors, mainly O2.

Question 17

Bronchial circulation

Answer 17

The blood supply to the conducting airways (which do not participate in gas exchange) and is a very small fraction of the pulmonary blood flow.

Question 18

Spirometer

Answer 18

A device used to measure static volumes of the lung. Typically, the subject is sitting and breathes into and out of the spirometer, displacing a bell. The volume displaced is recorded on calibrated paper.

Question 19

Tidal volume (VT)

Answer 19

Normal, quiet breathing involves inspiration and expiration of a tidal volume. Normal tidal volume is approximately 500 mL and includes the volume of air that fills the alveoli plus the volume of air that fills the airways.

Question 20

Inspiratory reserve volume

Answer 20

The additional volume of gas that can be inspired above tidal volume (approximately 3,000 mL).

Question 21

Expiratory reserve volume

Answer 21

The additional volume of gas that can be expired below tidal volume (approximately 1,200 mL).

Question 22

Residual volume (RV)

Answer 22

The volume of gas remaining in the lungs after a maximal forced expiration (approximately 1,200 mL). Cannot be measured by spirometry.

Question 23

Lung capacities

Answer 23

In addition to lung volumes, there are several lung capacities; each lung capacity includes two or more lung volumes.

Question 24

Inspiratory capacity (IC)

Answer 24

Composed of the tidal volume (~500 mL) plus the inspiratory reserve volume (~2,500 mL) and is approximately 3,500 mL (500 mL + 2,500 mL).

Question 25

Functional residual capacity (FRC)

Answer 25

Composed of the expiratory reserve volume (ERV) plus the residual volume (RV), or approximately 2,400 mL (1,200 mL + 1,200 mL).

FRC is the volume remaining in the lungs after a normal tidal volume is expired can can thought of as the equilibrium volume of the lungs.

Question 26

Vital capacity (VC)

Answer 26

Composed of the inspiratory capacity (IC) plus the expiratory reserve volume (ERV), or approximately 4,700 mL (3,500 mL + 1,200 mL).

Vital capacity if the volume that can be expired after maximal inspiration. Its value increases with body size, male gender, and physical conditioning and decreases with age.

Question 27

Total lung capacity (TLC)

Answer 27

Includes all of the lung volumes. It is the vital capacity (VC) plus the residual volume (RV), or 5,900 mL (4,700 mL + 1,200 mL).

Question 28

What are the two methods for measuring the functional residual capacity (FRC)?

Answer 28

1. Helium dilution.

2. Body plethysmograph.

Question 29

Dead space

Answer 29

The volume of the airways and lungs that does not participate in gas exchange.

Dead space is a general term that refers to both the anatomic dead space of the conducting airways and a functional, of physiologic, dead space.

Question 30

Anatomic dead space

Answer 30

The volume of the conducting airways including the nose (and/or mouth), trachea, bronchi, and bronchioles.

It does not include the respiratory bronchioles and alveoli.

Question 31

Physiologic dead space

Answer 31

The concept of physiologic dead space is more abstract than anatomic dead space. By definition, the physiologic dead space is the total volume of the lungs that does not participate in gas exchange.

Physiologic dead space includes the anatomic dead space of the conducting airways plus a functional dead space in the alveoli.

The functional dead space can be thought of as ventilated alveoli that do not participate in gas exchange. The most important reason that alveoli do not participate in gas exchange is a mismatch of ventilation and perfusion, or so-called ventilation/perfusion defect, in which ventilated alveoli are not perfused by pulmonary capillary blood.

Question 32

Functional dead space

Answer 32

Can be thought of as ventilated alveoli that do not participate in gas exchange. The most important reason that alveoli do not participate in gas exchange is a mismatch of ventilation and perfusion, or so-called ventilation/perfusion defect, in which ventilated alveoli are not perfused by pulmonary capillary blood.

Question 33

Ventilation/perfusion defect

Answer 33

Ventilated alveoli are not perfused by pulmonary capillary blood

Question 34

Ventilation rate

Answer 34

The volume of air moved into and out of the lungs per unit of time. Ventilation rate can be expressed either as the minute ventilation or as the alveolar ventilation.

Question 35

Minute ventilation

Answer 35

The total rate of air movement into or out of the lungs. per minute.

Question 36

Alveolar ventilation

Answer 36

The total rate of air movement into or out of the lungs per minute (minute ventilation) corrected for the physiologic dead space.

Question 37

Alveolar ventilation equation

Answer 37

The fundamental relationship of respiratory physiology and describes the inverse relationship between alveolar ventilation and alveolar PCO2 (PACO2).

Describes the dependence of alveolar and arterial PCO2 on alveolar ventilation.

A critical point to be understood from the alveolar ventilation equation is that if CO2 production is constant, then PACO2 is determined by alveolar ventilation.

An additional critical point, which is not immediately evident from the equation, is that because CO2 always equilibrated between pulmonary capillary blood and alveolar gas, the arterial PCO2 (PaCO2) always equals the alveolar PCO2 (PACO2).

Question 38

PCO2

Answer 38

Partial pressure of carbon dioxide.

Question 39

PaCO2

Answer 39

Partial pressure of arterial carbon dioxide.

Question 40

PACO2

Answer 40

Partial pressure of alveolar carbon dioxide.

Question 41

Alveolar gas equation

Answer 41

Used to predict alveolar PO2, based on the alveolar PCO2.

Question 42

Forced vital capacity (FVC)

Answer 42

The total volume of air that can be forcibly expired after a maximal expiration.

Question 43

Forced expiratory volume 1 (FEV1)

Answer 43

The volume of air that can be forcibly expired in the first second. By the second second, FEV2, and by the third, FEV3. Normally, the entire vital capacity can be forcibly expired in three seconds.

Question 44

FEV1/FVC

Answer 44

The fraction of the vital capacity that can be expired in the first second, FEV1/FVC, can be used to differentiate among diseases.

In a normal person, FEV1/FVC is approximately 0.8, meaning that 80% of the vital capacity can be expired in the first second of forced expiration.

Question 45

FEV1/FVC (obstructive lung diseases)

Answer 45

In obstructive lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD), both FVC and FEV1 are decreased, but FEV1 is decreased more than FVC. Thus, FEV1/FVC is also decreased, which is typical of airway obstruction with its increased resistance expiratory air flow.

Question 46

FEV1/FVC (restrictive lung diseases)

Answer 46

In restrictive lung diseases, such as fibrosis, both FVC and FEV1 are decreased, bu FEV1 is decreased less than FVC. Thus, FEV1/FVC is actually increased.

Question 47

Diaphragm

Answer 47

The most important muscle for inspiration. When the diaphragm contracts, the abdominal contents are pushed downward and the ribs are lifted upward and outward. These changes produce an increase in intrathoracic volume, which lowers intrathoracic pressure and initiates the flow of air into the lungs.

During exercise, when breathing frequency and tidal volume increases, the external intercostal muscles and accessory muscles may also be used for more vigorous inspiration.

Question 48

Muscles of expiration

Answer 48

Expiration normally is a passive process. Air is driven out of the lungs by the reverse pressure gradient between the lungs and the atmosphere until the system reaches its equilibrium point.

During exercise or in diseases in which airway resistance is increased (e.g., asthma), the expiratory muscles may aid the expiratory process. The muscles of expiration include the abdominal muscles, which compress the abdominal cavity and push the diaphragm up, and the internal intercostal muscles, which pull the ribs downward and inward.

Question 49

Compliance

Answer 49

The concept of compliance has the same meaning in the respiratory system as it has in the cardiovascular system: Compliance describes the distensibility of the system.

In the respiratory system, the compliance of the lungs and the chest wall is of primary interest.

Recall that compliance is a measure of how volume changes as a result of a pressure change. Thus, lung compliance describes the change in lung volume for a given change in pressure.

Question 50

Elastance

Answer 50

The elastic properties of the lungs and chest wall.

The compliance of the lungs and chest wall is inversely correlated with elastance.

Question 51

Transmural pressure

Answer 51

The pressure across a structure.

For example, transpulmonary pressure is the difference between intra-alveolar pressure and intrapleural pressure. (The intrapleural space lies between the lungs and the chest wall.)

Question 52

Intrapleural space

Answer 52

The space between the lungs and the chest wall.

Question 53

Pressure-volume loop

Answer 53

The sequence of inflation of the lung followed by deflation produces a pressure-volume loop.

Question 54

Hysteresis

Answer 54

An unusual feature of the pressure-volume loop for the air-filled lung is that the slops of the relationships for inspiration and expiration are different (i.e., hysteresis).

Question 55

What happens when the volume in the combined lung and chest-wall system is equal to functional residual capacity (FRC)?

Answer 55

When the volume is equal to functional residual capacity (FRC), the combined lung and chest-wall system is at equilibrium. Airway pressure is equal to atmospheric pressure, which is called zero.

Question 56

What happens when the volume in the combined lung and chest-wall system is less than functional residual capacity (FRC)?

Answer 56

When the volume in the system is less than FRC (i.e., the subject make a forced expiration into the spirometer), there is less volume in the lungs and the collapsing (elastic) force of the lungs is smaller. The expanding force on the chest wall is greater, however, and the combined lung and chest-wall system “wants” to expand.

Question 57

What happens when the volume in the combined lung and chest-wall system is greater than functional residual capacity (FRC)?

Answer 57

When the volume in the system is greater than FRC (i.e., the subject inspires from the spirometer), there is more volume in the lungs and the collapsing (elastic) force of the lungs is greater. The expanding force on the chest wall is smaller, however, and the combined lung and chest-wall system “wants” to collapse.

Question 58

Emphysema (increase lung compliance)

Answer 58

Emphysema, a component of COPD, is associated with loss of elastic fibers in the lungs. As a result, the compliance of the lungs increases. (Recall again the inverse relationship between elastance an compliance)

The combined lung and chest-wall system seeks a new higher functional residual capacity (FRC), where the two opposing forces can be balanced; the new intersection point, where airway pressure is zero, is increased.

A patient with emphysema is said to breath at higher lung volumes (in recognition of the higher FRC) and will have a barrel-shaped chest.

Question 59

Fibrosis (decreased lung compliance)

Answer 59

Fibrosis, a so-called restrictive disease, is associated with stiffening of lung tissues and decreased compliance. A decrease in lung compliance is associated with a decreased slope of the volume-versus-pressure curve for the lung.

To reestablish balance, the lung and chest-wall system will seek a new lower functional residual capacity (FRC); the new intersection point, where airway pressure is zero, is decreased.

Question 60

Surface tension of alveoli

Answer 60

Because of the inverse relationship with radius, a large alveolus (one with a large radius) will have a low collapsing pressure and therefore will require only minimal pressure to keep it open.

On the other hand, a small alveolus (one with a small radius) will have a high collapsing pressure and require more pressure to keep it open.

Yet from the standpoint of gas exchange, alveoli need to be as small as possible to increase their total surface area relative to volume.

This fundamental conflict is solved by surfactant.

Question 61

How do small alveoli remain open under high collapsing pressure?

Answer 61

The answer to this question is found in surfactant, a mixture of phospholipids that line the alveoli and reduce their surface tension. By reducing surface tension, surfactant reduces the collapsing pressure for a given radius.

Question 62

What cell type synthesizes surfactant?

Answer 62

Type II alveolar cells.

Question 63

What is the most important component of surfactant?

Answer 63

Dipalmitoyl phosphatidylcholine (DPPC). The mechanism by which DPCC reduces surface tension is based on the amphipathic nature of the phospholipid molecules.

Question 64

What are the advantages of surfactant for pulmonary function?

Answer 64

1. Reducing the surface tension of alveoli, allow for smaller radiuses and more efficient gas exchange.
2. Increased lung compliance, which reduces the work of expanding the lungs during inspiration.

Question 65

Neonatal respiratory distress syndrome

Answer 65

In the developing fetus, surfactant synthesis begins as early as gestational week 24 and it is almost always present by week 35. The more prematurely the infant is born, the less it is likely that surfactant will be present. Infants born before gestational week 24 will never have surfactant, and infants born between weeks 24 and 35 will have uncertain surfactant status.

Question 66

Atelectasis

Answer 66

A complete or partial collapse of the entire lung or area (lobe) of the lung. It occurs when the tiny air sacs (alveoli) within the lung become deflated or possibly filled with alveolar fluid. Atelectasis is one of the most common breathing (respiratory) complications after surgery.

Collapses alveoli are not ventilated and therefore cannot participate in gas exchange (this is called a shunt).; consequently, hypoxemia develops.

Question 67

What happens when there is no surfactant in the lungs?

Answer 67

1. Collapsed alveoli (atelectasis) and impaired gas exchange.
2. Without surfactant, lung compliance will be decreased and the work of inflating the lungs during breathing will be increased.

Question 68

What is the site of highest airway resistance?

Answer 68

Medium-size bronchi.

Question 69

What can alter airway resistance?

Answer 69

1. Airway diameter.
2. Autonomic nervous system.
3. Lung volume.
4. Viscosity of inspired air.

Question 70

What are the three phases of the breathing cycle?

Answer 70

1. Rest (the period between breaths).
2. Inspiration.
3. Expiration.

Question 71

Breathing cycle: Rest

Answer 71

Rest is the period between breathing cycles when the diaphragm is at its equilibrium position. At rest, no air is moving into or out of the lungs. Alveolar pressure equals atmospheric pressure, and because there is no pressure difference, there is no airflow. Intrapleural pressure is negative.

The volume present in the lungs at rest is the equilibrium volume, or functional residual capacity (FRC), which, by definition, is the volume remaining in the lungs after a normal expiration.

Question 72

Breathing cycle: Inspiration

Answer 72

During inspiration, the diaphragm contracts, causing the volume of the thorax to increase. As lung volume increases, the pressure in the lungs must decrease. Air flows into the lungs until, at the end of inspiration, alveolar pressure is once again equal to atmospheric pressure (i.e., no pressure gradient).

The volume of air inspired in one breath is the tidal volume (VT), which is approximately 0.5 L. Thus, the volume present in the lungs at the end of normal inspiration is the functional residual capacity (FRC) plus one tidal volume (FRC + VT).

During inspiration, intrapleural pressure becomes even more negative.

Question 73

Breathing cycle: Expiration

Answer 73

Normally, expiration is a passive process. Alveolar pressure becomes positive (higher than atmospheric pressure) because the elastic forces of the lungs compress the greater volume of air in the alveoli. When alveolar pressure increases above atmospheric pressure, air flows out of the lungs and the volume in the lungs returns to functional residual capacity (FRC).

Question 74

Forced expiration

Answer 74

In a normal person, the forced expiration makes the pressures in the lungs and airways very positive. Both. airway and alveolar pressures are raised to much higher values than those occurring during passive expiration. Contraction of the expiratory muscles also raises intrapleural pressure, now to a positive value. However, this does not force the lungs to collapse.

In a person with emphysema, however, forced expiration may cause airways to collapse. To prevent this, people with emphysema learn to expire slowly with pursed lips, which creates a high resistance at the mouth and raises airway pressure, thus preventing the reversal of the transmural pressure gradient across the large airways and preventing their collapse.

Question 75

Respiratory gas exchange

Answer 75

The diffusion of O2 and CO2 in the lungs and in the peripheral tissues. O2 is transferred from alveolar gas into pulmonary capillary blood and, ultimately, delivered to the tissues, where it diffuses from systemic capillary blood into the cells. CO2 is delivered from the tissues to venous blood, to pulmonary capillary blood, and is transferred t alveolar gas to be expired.

Question 76

Does the partial pressure of a gas in liquid phase equal its partial pressure in the gas phase?

Answer 76

Yes. This can be deduced from Henry’s law for concentrations of dissolved gases.

Question 77

How does the transfer of gases across cell membranes or capillary walls occur?

Answer 77

Simple diffusion.

Question 78

Two special points regarding diffusion of gases.

Answer 78

1. The driving force for diffusion of a gas is the partial pressure difference of the gas ([delta]P) across teh membrane, not the concentration difference.
2. The diffusion coefficient of a gas (D) is a combination of the usual diffusion coefficient, which depends on molecular weight, and the solubility of the gas.

Question 79

Lung diffusing capacity (DL)

Answer 79

Combines the diffusion coefficient of the gas (D), the surface area of the membrane (A), and the thickness of the membranes ([delta]x). It also takes into account the time required for the gas to combine with proteins in pulmonary capillary blood.

In emphysema, DL decreases because destruction of alveoli results in a decreased surface area for gas exchange.

In fibrosis or pulmonary edema, DL decreases because the diffusion distance (membrane thickness or interstitial volume) increases.

In anemia, DL decreases because the amount of hemoglobin in red blood cells is reduced (recall that DL includes the protein-binding component of O2 exchange).

Question 80

What are the three forms of gases in solution?

Answer 80

In alveolar air, there is one form of gas, which is expressed as partial pressure. However, in solutions such as blood, gases are carried in additional forms. In solution, gas may be dissolved, it may be bound to proteins, or it may be chemically modified.

It is important to understand that the total gas concentration in solution is the sum of dissolved gas plus bound gas plus chemically modified gas.

Question 81

Summary of gas transport in the lungs

Answer 81

The pulmonary capillaries are perfused with blood from the right heart (the equivalent of mixed venous blood). Gas exchange then occurs between alveolar gas and the pulmonary capillary: O2 diffuses from alveolar gas into pulmonary capillary blood, and CO2 diffuses from pulmonary capillary blood into alveolar gas. The blood leaving the pulmonary capillary is delivered to the left heart and becomes systemic arterial blood.

Question 82

Arterialized

Answer 82

The blood that leaves the pulmonary capillaries has been arterialized (oxygenated) and will become systemic arterial blood.

Question 83

Physiologic shunt

Answer 83

The small fraction of pulmonary blood flow that bypasses the alveoli and therefore is not arterialized.

Question 84

Ventilation/perfusion defect

Answer 84

The physiologic shunt is increased in several pathologic conditions. When the size of the shunt increases, equilibration between alveolar gas and pulmonary capillary blood cannot adequately occur and pulmonary capillary blood is not fully arterialized.

Question 85

Exchange processes in systemic tissues

Answer 85

Systemic arterial blood is delivered to the tissues, where O2 diffuses from systemic capillaries into the tissues and is consumed, producing CO2, which diffuses from the tissues into the capillaries. This gas exchange in the tissues converts system arterial blood to mixed venous blood, which then leaves the capillaries, returns to the right heart, and is delivered to the lungs.

Question 86

Diffusion-limited gas exchange

Answer 86

The total amount of gas transported across the alveolar-capillary barrier is limited by the diffusion process.

In these cases, as long as the partial pressure gradient for the gas is maintained, diffusion will continue along the length of the capillary.

Question 87

Perfusion-limited gas exchange

Answer 87

The total amount of gas transported across the alveolar-capillary barrier is limited by blood flow (i.e., perfusion) through the pulmonary capillaries.

In perfusion-limited exchange, the partial pressure gradient is not maintained, and in this case, the only way to increase the amount of gas transported is by increasing blood flow.

Question 88

Perfusion-limited O2 transport

Answer 88

In the lungs of a normal person at rest, O2 transfer form alveolar air into pulmonary capillary blood is perfusion limited (although not to the extreme that N2O is perfusion limited).

Another way of describing perfusion-limited O2 exchange is to say that pulmonary blood flow determines net O2 transfer. Thus, increases in pulmonary blood flow (e.g., during exercise) will increase the total amount of O2 transported, and decreases in pulmonary blood flow will decrease the total amount transported.

Question 89

Diffusion-limited O2 transport

Answer 89

In certain pathologic conditions (e.g., fibrosis) and during strenuous exercise, O2 transfer becomes diffusion limited. for example, in fibrosis the alveolar wall thickens, increasing the diffusion distance for gases and decreasing lung diffusion capacity (DL).

Question 90

What are the two forms that oxygen is carried in blood?

Answer 90

1. Dissolved.

2. Bound to hemoglobin.

Question 91

Dissolved O2

Answer 91

One of the two forms that oxygen in carried in the blood. Dissolved O2 is free in solution and accounts for approximately 2% of the total O2 content of blood.

Recall that dissolved O2 is the only form of O2 that produces a partial pressure, which, in turn, drives O2 diffusion.

Dissolved O2 is grossly insufficient to meet the demands of the tissues.

Question 92

O2 bound to hemoglobin

Answer 92

The remaining 98% of the total O2 content of blood is reversibly bound to hemoglobin inside the red blood cells (only 2% is dissolved).

Question 93

Hemoglobin

Answer 93

A globular protein consisting of four subunits. Each subunit contains a heme moiety, which is an iron-binding porphyrin, and a poplypeptide chain, which is designated either alpha or beta.

For the subunits to bind O2, iron in the heme moieties must be in the ferrous state (Fe2+).

Question 94

Adult hemoglobin

Answer 94

Adult hemoglobin (hemoglobin A) is called (alpha)2(beta)2; two of the subunits have alpha chains and two have beta chains. Each subunit can bind one molecule of O2, for a total of four molecules of O2 per molecule of hemoglobin.

The percent of heme groups bound to O2 is called percent (%) saturation; thus 100% saturation means that all four heme groups are bound to O2.

Question 95

Oxyhemoglobin

Answer 95

Oxygenated hemoglobin.

Question 96

Deoxyhemoglobin

Answer 96

Deoxygenated hemoglobin.

Question 97

Methemoglobin

Answer 97

If the iron component of the heme moieties is in the ferric (Fe3+) state (rather than the normal ferrous [Fe2+] state), it is called methemoglobin.

Methemoglobin does not bind O2.

Question 98

Fetal hemoglobin (hemoglobin F, HbF)

Answer 98

In fetal hemoglobin, the two beta chains are replaced by gamma chains, giving it the designation of (alpha)2(gamma)2.

The physiologic consequence of this modification is that HbF has a higher affinity for O2 than hemoglobin A, facilitating O2 movement from the mother to the fetus.

HbF is the normal variant in the fetus and is gradually replaced by hemoglobin A within the first year of life.

Question 99

Hemoglobin S

Answer 99

Hemoglobin S is an abnormal variant of hemoglobin that causes sickle cell disease. In hemoglobin S, the alpha subunits are normal and the beta subunits are abnormal, giving it the designation (alpha)^S_2(beta)^S_2.

In its deoxygenated form hemoglobin S forms sickle-shaped rods in the red blood cells, distorting the shape of the red blood cells (i.e., sickling them).

This deformation of the red blood cells can result in occlusion of small blood vessels, causing many of the symptoms of sickle cell crisis (e.g., pain).

The O2 affinity of hemoglobin S is less than the O2 affinity of hemoglobin A.

Question 100

How is the O2 content of blood primarily determined?

Answer 100

Because the majority of O2 transported in the blood is reversibly bound to hemoglobin, the O2 content of blood is primarily determined by the hemoglobin concentration and by the O2-binding capacity of that hemoglobin.

Question 101

O2-binding capacity of hemoglobin

Answer 101

The maximum amount of O2 that can be bound to hemoglobin per volume of blood, assuming that hemoglobin is 100% saturated (i.e., all four heme groups on each molecule of hemoglobin are bound to O2).

Question 102

O2 content

Answer 102

The actual amount of O2 per volume of blood. It can be calculated from the O2-binding capacity of hemoglobin and the percent saturation of hemoglobin, plus any dissolved O2.

Question 103

How is the amount of O2 delivered to the tissues determined?

Answer 103

It is determined by blood flow and the O2 content of blood. In terms of the whole organism, blood flow is considered to be cardiac output. The O2 content of blood is the sum of dissolved O2 (2%) and O2-hemoglobin (98%).

Question 104

O2-hemoglobin dissociation curve

Answer 104

Percent saturation of hemoglobin is a function of the partial pressure of oxygen (PO2) in blood. The most striking feature of this curve is its sigmoidal shape. In other words, the percent saturation of heme sites does not increase linearly as PO2 increases. Rather, it increases steeply as PO2 increases from zero to approximately 40 mm Hg, and it then levels off between 50 mm Hg and 100 mm Hg.

The shape of the steepest portion of the curve is the result of a change in affinity of the heme groups for O2 as each successive O2 molecule binds: Binding of the first molecule of O2 to a heme group increases affinity for the second O2 molecule, and so on, until the fourth molecule, where the last heme group will have the highest affinity.

This phenomenon is called positive cooperativity.

Question 105

Why is O2 loaded into pulmonary capillary blood from alveolar gas and unloaded from systemic capillaries into the tissues?

Answer 105

At the highest values of PO2 (i.e., in the systemic arterial blood) the affinity of hemoglobin for O2 is highest; at lower values of PO2 (i.e., in mixed venous blood), affinity for O2 is lower.